journal article·2025-05-22Open access

Comparative Antioxidant and Anti-Inflammatory Activity of Ellagic Acid and Juglans regia L. in Collagenase-Induced Osteoarthritis in Rats

Alina Hanga-Farcas, Luminita Fritea, Gabriela Adriana Filip, Simona Clichici, Laura Gratiela Vicas, Adina Frum, Mariana Eugenia Muresan

Applied Sciences· Volume 15· Issue 11

Abstract

Osteoarthritis (OA), the most common degenerative pathology of the joints, affects mainly elderly people, and it is one of the most important factors causing disability. This study aimed to assess the effect of Juglans regia L. on rats with collagenase-induced knee osteoarthritis comparative with groups with the same disease treated with ellagic acid (EA), indomethacin as positive control and vehicle as negative control. After 2 and 4 weeks of treatment, blood samples were collected in order to evaluate the oxidative stress and inflammation, as well as RANKL and hydroxyproline levels. The results showed that EA improved the systemic antioxidant defense (p < 0.05), decreased the interleukin-6 (IL-6) secretion (p < 0 < 0.05) and RANKL levels (p < 0.01 and p < 0.001) at the same time enhancing hydroxyproline values, particularly after 2 weeks of treatment (p < 0.01). JR extract especially maintained low values of RANKL (p < 0.05) and hydroxyproline levels (p < 0.05), indicating a partial chondroprotective effect compared to EA. In conclusion, the use of EA and JR extract can improve some parameters of bone regeneration in experimental osteoarthritis, suggesting beneficial effects in articular inflammatory diseases. However, further studies are necessary to establish the optimum dose and time of treatment with both compounds in order to obtain optimal therapeutic results.
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Research context

OpenAlex topics: Pomegranate: compositions and health benefits · Bee Products Chemical Analysis · Phytase and its Applications

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Doctoral School of Biomedical Sciences, University of Oradea, 1 University Street, 410087 Oradea, Romania

Department of Preclinical Discipline, Faculty of Medicine and Pharmacy, University of Oradea, 10, 1 December Square, 410073 Oradea, Romania

Department of Physiology, Iuliu Hatieganu University of Medicine and Pharmacy, 8 Victor Babes Street, 400347 Cluj-Napoca, Romania

Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, 10, 1 December Square, 410073 Oradea, Romania

Preclinical Department, Faculty of Medicine, Lucian Blaga University of Sibiu, 550012 Sibiu, Romania

Funding

the University of Oradea

References (51)

Show source-provided references
1. Di Francesco, M., Fragassi, A., Pannuzzo, M., Ferreira, M., Brahmachari, S., and Decuzzi, P. (2022). Management of Osteoarthritis: From Drug Molecules to nano/micromedicines. WIREs Nanomed. Nanobiotechnol., 14.10.1002/wnan.1780 ↗
2. Articular Cartilage: From Formation to Tissue Engineering10.1039/C6BM00068A ↗
3. The Basic Science of Articular Cartilage: Structure, Composition, and Function10.1177/1941738109350438 ↗
4. Synovial Tissue Metabolomic Profiling Reveal Biomarkers of Synovial Inflammation in Patients with Osteoarthritis10.1016/j.ocarto.2022.100295 ↗
5. The Role of Synovial Macrophages and Macrophage-Produced Cytokines in Driving Aggrecanases, Matrix Metalloproteinases, and Other Destructive and Inflammatory Responses in Osteoarthritis10.1186/ar2099 ↗
6. A Roadmap to Target Interleukin-6 in Osteoarthritis10.1093/rheumatology/keaa248 ↗
7. Di Cicco, G., Marzano, E., Mastrostefano, A., Pitocco, D., Castilho, R.S., Zambelli, R., Mascio, A., Greco, T., Cinelli, V., and Comisi, C. (2024). The Pathogenetic Role of RANK/RANKL/OPG Signaling in Osteoarthritis and Related Targeted Therapies. Biomedicines, 12.10.3390/biomedicines12102292 ↗
8. Liang, J., Liu, L., Feng, H., Yue, Y., Zhang, Y., Wang, Q., and Zhao, H. (2023). Therapeutics of Osteoarthritis and Pharmacological Mechanisms: A Focus on RANK/RANKL Signaling. Biomed. Pharmacother., 167.10.1016/j.biopha.2023.115646 ↗
9. Stabilization of the Collagen Triple Helix by O-Methylation of Hydroxyproline Residues10.1021/ja800225k ↗
10. Intra-Articular Injection of Collagenase in the Knee of Rats as an Alternative Model to Study Nociception Associated with Osteoarthritis10.1186/ar4436 ↗
11. Impact of Olive Leaf Extract on Pain Management and Functional Improvement in Elderly Patients with Knee Osteoarthritis: A Randomized Controlled Trial10.1016/j.explore.2025.103136 ↗
12. Potential Metabolites of Arecaceae Family for the Natural Anti-Osteoarthritis Medicine: A Review10.1016/j.heliyon.2022.e12039 ↗
13. A Review Focusing on the Benefits of Plant-Derived Polysaccharides for Osteoarthritis10.1016/j.ijbiomac.2022.12.153 ↗
14. Management of Pain and Inflammation Through Natural Products in Individuals With Knee Osteoarthritis: A Systematic Review10.1016/j.hermed.2024.100851 ↗
15. A Standardized Nutraceutical Supplement Contributes to Pain Relief, Improves Quality of Life and Regulates Inflammation in Knee Osteoarthritis Patients; A Randomized Clinical Trial10.1016/j.heliyon.2023.e20143 ↗
16. Hanga-Farcaș, A., Miere (Groza), F., Filip, G.A., Clichici, S., Fritea, L., Vicaș, L.G., Marian, E., Pallag, A., Jurca, T., and Filip, S.M. (2023). Phytochemical Compounds Involved in the Bone Regeneration Process and Their Innovative Administration: A Systematic Review. Plants, 12.10.20944/preprints202304.0484.v1 ↗
17. Bezerra, J.J.L., and Oliveira, A.F.M.D. (2024). Exploring the Therapeutic Potential of Brazilian Medicinal Plants for Anti-Arthritic and Anti-Osteoarthritic Applications: A Comprehensive Review. Biocatal. Agric. Biotechnol., 56.10.1016/j.bcab.2024.103064 ↗
18. Lin, Z., Lin, C., Fu, C., Lu, H., Jin, H., Chen, Q., and Pan, J. (2020). The Protective Effect of Ellagic Acid (EA) in Osteoarthritis: An in Vitro and in Vivo Study. Biomed. Pharmacother., 125.10.1016/j.biopha.2020.109845 ↗
19. Al-Shammari, S.K., Al-Nouri, D.M., Arzoo, S., and Al-Harbi, L.N. (2023). Effect of Different Nuts Oil Consumption on Morphological Features and Some Biomarkers of Inflammation in Adjuvant-Induced Arthritis (AIA) Rat Model. Appl. Sci., 13.10.3390/app13053318 ↗
20. Javed, K., Rakha, A., Butt, M.S., Faisal, M.N., Tariq, U., and Saleem, M. (2022). Evaluating the Anti-arthritic Potential of Walnut (Juglans Regia L.) in FCA Induced Sprague Dawley Rats. J. Food Biochem., 46.10.1111/jfbc.14327 ↗
21. Javed, K., Rakha, A., Butt, M.S., and Faisal, M.N. (2022). Probing the Antioxidant Potential of Juglans Regia (Walnut) against Arthritis-induced Oxidative Stress in Sprague Dawley Rats. J. Food Biochem., 46.10.1111/jfbc.14082 ↗
22. Preclinical Rodent Models of Arthritis and Acute Inflammation Indicate Immunomodulatory and Anti-Inflammatory Properties of Juglans Regia Extracts10.1155/2022/1695701 ↗
23. Dong, H., Cao, Y., Zou, K., Shao, Q., Liu, R., Zhang, Y., Pan, L., and Ning, B. (2024). Ellagic Acid Promotes Osteoblasts Differentiation via Activating SMAD2/3 Pathway and Alleviates Bone Mass Loss in OVX Mice. Chem. Biol. Interact., 388.10.1016/j.cbi.2023.110852 ↗
24. Hanga-Farcas, A., Fritea, L., Filip, G.A., Clichici, S., Vicas, L.G., Toma, V.-A., Marian, E., Gligor, F.G., Abu Dayyih, W., and Muresan, M.E. (2024). The Influence of Juglans Regia L. Extract and Ellagic Acid on Oxidative Stress, Inflammation, and Bone Regeneration Biomarkers. Int. J. Mol. Sci., 25.10.3390/ijms252312577 ↗
25. Astounding the Synergistic Interplay of Walnuts in Combating Inflammation and Oxidative Damage10.1016/j.jff.2024.106292 ↗
26. Collagenase and Sodium Iodoacetate-Induced Experimental Osteoarthritis Model in Sprague Dawley Rats10.3923/ajsr.2009.167.179 ↗
27. Viburnum Opulus Fruit Extract-Capped Gold Nanoparticles Attenuated Oxidative Stress and Acute Inflammation in Carrageenan-Induced Paw Edema Model10.1080/17518253.2022.2061872 ↗
28. Anti-Inflammatory, and Anti-Arthritic Effects by the Twigs of Cinnamomum Cassia on Complete Freund’s Adjuvant-Induced Arthritis in Rats10.1016/j.jep.2021.114209 ↗
29. Anti-Inflammatory and Antioxidant Properties of Jervine, a Sterodial Alkaloid from Rhizomes of Veratrum Album10.1016/j.phymed.2018.06.035 ↗
30. Assessment of Movement-Evoked Pain in Osteoarthritis by the Knee-Bend and CatWalk Tests: A Clinically Relevant Study10.1016/j.jpain.2008.05.012 ↗
31. Intra-Articular Delivery of Flurbiprofen Sustained Release Thermogel: Improved Therapeutic Outcome of Collagenase II-Induced Rat Knee Osteoarthritis10.1080/10717544.2020.1787555 ↗
32. Injury of Primary Afferent Neurons May Contribute to Osteoarthritis Induced Pain: An Experimental Study Using the Collagenase Model in Rats10.1016/j.joca.2015.02.010 ↗
33. Ellagic Acid Protects Type II Collagen Induced Arthritis in Rat via Diminution of IKB Phosphorylation and Suppression IKB-NF-kB Complex Activation: In Vivo and in Silico Study10.1007/s10787-022-01022-x ↗
34. New Developments in Osteoarthritis and Cartilage Biology10.1016/j.coph.2016.02.009 ↗
35. Global, Regional and National Burden of Osteoarthritis 1990-2017: A Systematic Analysis of the Global Burden of Disease Study 201710.1136/annrheumdis-2019-216515 ↗
36. Villagrán-Andrade, K.M., Núñez-Carro, C., Blanco, F.J., and De Andrés, M.C. (2024). Nutritional Epigenomics: Bioactive Dietary Compounds in the Epigenetic Regulation of Osteoarthritis. Pharmaceuticals, 17.10.20944/preprints202408.0100.v1 ↗
37. Medicinal Plants and Their Secondary Metabolites in Alleviating Knee Osteoarthritis: A Systematic Review10.1016/j.phymed.2022.154347 ↗
38. Exploring the Potential of Moringa Oleifera in Managing Bone Loss: Insights from Preclinical Studies10.7150/ijms.103241 ↗
39. Santiago, L.Â.M., Ataíde, A.C.S., De Araújo Morais, D., Da Silva Lima, A., Dos Santos Martins, N., Dourado, A.V.C.A., Ribeiro, R.M., Lima-Neto, L.G., De Sá Sousa, J.C., and Da Rocha, C.Q. (2023). Bixa Orellana Ethyl Acetate Fraction and Its Isolated Compound Ellagic Acid Attenuate the Progression of MIA-Induced Osteoarthritis in Rat Knees. Biomed. Pharmacother., 168.10.1016/j.biopha.2023.115644 ↗
40. Walnut Extract (Juglans Regia L.) and Its Component Ellagic Acid Exhibit Anti-Inflammatory Activity in Human Aorta Endothelial Cells and Osteoblastic Activity in the Cell Line KS48310.1017/S0007114507837421 ↗
41. Guava Leaf Extract Suppresses Osteoarthritis Progression in a Rat Anterior Cruciate Ligament Transection Model10.1002/fsn3.601 ↗
42. Ellagic Acid Alleviates Adjuvant Induced Arthritis by Modulation of Pro- and Anti-Inflammatory Cytokines10.5114/ceji.2016.65132 ↗
43. Effects of Pomegranate (Punica Granatum L.) Peel Extract Supplementation on Serum Lipid Profile and Oxidative Stress in Obese Women with Knee Osteoarthritis: A Double Blind, Randomized, Placebo Controlled Study10.1016/j.aimed.2020.05.001 ↗
44. Epimedin C Alleviated Osteoarthritis Development by Regulating Chondrocyte Nrf2-Mediated NLRP3 Inflammasome Axis10.1016/j.heliyon.2024.e40458 ↗
45. Extracts of Oldenlandia Diffusa Protects Chondrocytes via Inhibiting Apoptosis and Associated Inflammatory Response in Osteoarthritis10.1016/j.jep.2023.116744 ↗
46. Urolithin B Reduces Cartilage Degeneration and Alleviates Osteoarthritis by Inhibiting Inflammation10.1039/D3FO03793B ↗
47. Ellagic Acid Attenuates Interleukin-1β-Induced Oxidative Stress and Exerts Protective Effects on Chondrocytes through the Kelch-like ECH-Associated Protein 1 (Keap1)/Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) Pathway10.1080/21655979.2022.2059995 ↗
48. Bioavailable Turmeric Extract for Knee Osteoarthritis: A Randomized, Non-Inferiority Trial versus Paracetamol10.1186/s13063-021-05053-7 ↗
49. Elbeialy, A., Elabd, H., Shahen, A., and Ibrahim, R. (2022). Hydroxyproline as a New Biomarker to Differentiate Osteoarthritis from Rheumatoid Arthritis in the Early Stages. Res. Sq.10.21203/rs.3.rs-1445583/v2 ↗
50. Metabolic Regulatory and Anti-Oxidative Effects of Modified Bushen Huoxue Decoction (补肾活血方) on Experimental Rabbit Model of Osteoarthritis10.1007/s11655-011-0727-x ↗
51. Triphala Exhibits Anti-Arthritic Effect by Ameliorating Bone and Cartilage Degradation in Adjuvant-Induced Arthritic Rats10.3109/08820139.2015.1017047 ↗